1,056 research outputs found
Applied algebra and number theory: essays in honour of Harald Niederreiter on the occasion of his 70th birthday
No full text"Harald Niederreiter's pioneering research in the field of applied algebra and number theory has led to important and substantial breakthroughs in many areas, including finite fields and their application areas as coding theory and cryptography as well as uniform distribution and quasi-Monte Carlo methods. He is author of more than 350 research papers and 10 books"-
2. Networks, states and empires in the Baltic Region
No full textMain author Kristian Gerner. Harald Runblom author of boxes on The Vikings and The Hansa.</p
Implication de la protéase de l'Adénovirus dans le désassemblage partiel de la capside et le relargage de la protéine VI
No full textL’Adénovirus est un virus non-enveloppé qui entre dans les cellules par endocytose après reconnaissance aux récepteurs cellulaires. Pendant cette étape d’entrée, la capside subit un désassemblage partiel à l’intérieur de l’endosome qui permet la libération de la protéine VI. Cette protéine est responsable de la lyse de la membrane de l’endosome, permettant ainsi à la capside de s’échapper de l’endosome pour accéder au cytosol et être transportée vers l’enveloppe nucléaire via les microtubules. Les mécanismes cellulaires et / ou viraux permettant ce désassemblage partiel ne sont pas entièrement compris. Le projet vise à investiguer le rôle potentiel de la protéase de l’Adénovirus (AVP) dans cette étape d’entrée. L’AVP est une protéase à cystéine produite dans une forme inactive et incorporée dans les capsides comme une protéine de liaison à l’ADN, indépendamment de sa séquence. Une fois activée par deux cofacteurs, elle permet le clivage de différentes protéines via une réaction biochimique à une dimension. Cette étape, appelée maturation, se produit suite à / pendant l’assemblage de la capside dans la cellule infectée et rend la capside moins stable, ce qui est essentiel pour l’infectivité du virus. Un mutant de l’Adénovirus qui n’incorpore pas l‘AVP est donc composé de protéines non clivées et possède par conséquent une capside hyperstable. Ce mutant est ainsi incapable de libérer la protéine VI dans l’endosome et est dégradé par la voie lysosomale. Nous avons produit et purifié l’AVP afin de développer un test de maturation in vitro des protéines virales et apporter une meilleure compréhension de son rôle potentiel dans le désassemblage partiel de la capside. Nous avons identifié un nouveau site de clivage fonctionnel d’une protéine de la capside qui pourrait être un des déclencheurs de la libération de la protéine VI. Nous combinons des approches de biochimie et de biologie cellulaire afin de confirmer que l’activité de clivage de l’AVP facilite l’entrée du virus.The Adenovirus is a non-enveloped virus entering the cells by endocytosis after attachment to cell receptors. During entry, the capsid undergoes a partial disassembly inside the endosome, which is allowing the release of protein VI. This protein is responsible for the endosomal membrane damages that allow the capsid to escape the endosome to access the cytoplasm, to follow nuclear transport mediated by microtubules. The cellular and / or viral cues allowing this intra-endosomal disassembly are not fully understood. The project goal is to investigate the potential role of the Adenovirus protease (AVP) in this entry step. The AVP is produced as an inactive cysteine protease and is incorporated in the capsids as an unspecific DNA sequence binding protein. Once activated by two co-factors, it allows the cleavage of multiple proteins through a one dimensional biochemical reaction. This step, called maturation, is happening after / during the assembly of the capsids in the infected cell. It destabilizes the capsid, which is essential for the virus infectivity. An Adenovirus mutant, which is not incorporating the AVP, is composed of unprocessed proteins and thus, possesses a hyperstable capsid. Therefore, this mutant cannot release the protein VI in the endosome and thus, is degraded via the lysosomal pathway. We produced and purified the AVP to develop an in vitro maturation assay of the viral proteins, and bring a better understanding of its potential role in the partial disassembly of the capsid. We identified a new functional cleavage site of a capsid protein which could be one of the triggers of the protein VI release. We combined biochemical and cell biology approaches to confirm that the cleavage activity of the AVP is facilitating the virus entry
Role of capsid protein VI post-translational modifications in adenovirus host cell entry
No full textLes adénovirus sont des virus non enveloppés. Afin de pouvoir se répliquer ils doivent entrer dans leur cellule hôte et être transportés jusqu’au noyau pour pouvoir initier l’expression du génome viral. Pour ce faire le virus utilise les composants de sa capside. Parmi ses composants, la protéine VI, une protéine interne de capside, induit la rupture de l’endosome grâce à son hélice amphipatique en N-terminal de la protéine. Récemment, une autre fonction de cette protéine a été décrite durant l’entrée du virus, impliquant cette fois-ci le motif conservé PPxY de la protéine VI. En effet la mutation de ce motif conservé : mutant M1 (PPxYPGAA), diminue de 20 fois l’infection du virus par rapport au virus sauvage. Cette baisse d’infectiosité est liée à un défaut de transport et d’accumulation du virus au niveau du centre organisateur des microtubules (MTOC). Il se trouve que la mutation du motif PPxY conduit à une perte d’interaction de la protéine VI avec les ubiquitines ligase de la famille Nedd4, mais également à un défaut d’ubiquitylation de la protéine VI. Nous avons ainsi entrepris d’étudier le rôle de cette modification post-traductionnelle lors de l’entrée du virus dans la cellule, mais aussi, de manière plus générale, le rôle de la protéine VI. Ainsi nous avons mis en évidence le rôle de la protéine VI et de son motif PPxY dans l’activation du génome viral. Par ailleurs, nous avons identifié une lysine ubiquitylée de la protéine VI et produit un mutant : mutant M6, pour étudier le rôle de cette ubiquitylation. Nous avons enfin entrepris de caractériser l’entrée du virus en produisant et en utilisant des adénovirus mutants, dont le nouveau mutant M6Adenoviruses are non-enveloped viruses. In order to replicate they have to enter their host cell and be transported toward the nucleus to initiate the viral gene expression. This requires the involvement of viral capsids components. Among these components, protein VI, an inner capsid protein, can induce endosomal rupture, thanks to its amphipathic helix located at the N-terminus part of the protein. Recently, the involvement of a conserved PPxY motif in the Protein VI has also been described in viral entry. Indeed, mutation of this motif (PPxY PGAA) reduced infectivity of the mutant virus (M1 mutant) 20 folds compared to the wild type virus. This reduction of infectivity is related to a defect of transport and accumulation of viruses at the microtubule organizing center (MTOC) during virus entry. The mutation of PPxY motif leads to a loss of interaction between the protein VI and ubiquitin ligases from the Nedd4 family, and to a lack of protein VI ubiquitylation. The aim of this study was therefore to investigate the role of this posttranslational modification during virus entry, but also more generally the role of protein VI. In this work, we highlight the role of protein VI and its PPxY motif in the activation of the viral genome. Moreover, to investigate the ubiquitylation during virus entry we identify a lysine mutant of protein VI that lack ubiquitylation without altering the potential for interaction with ubiquitin ligases: the mutant M6. We then proceed to characterize the entry of the virus by producing and using mutant viruses, including this new mutant
Heterodimerization with Jun family members regulates c-Fos nucleocytoplasmic traffic
No full textc-Fos proto-oncoprotein forms AP-1 transcription complexes with heterodimerization partners such as c-Jun, JunB, and JunD. Thereby, it controls essential cell functions and exerts tumorigenic actions. The dynamics of c-Fos intracellular distribution is poorly understood. Hence, we have combined genetic, cell biology, and microscopic approaches to investigate this issue. In addition to a previously characterized basic nuclear localization signal (NLS) located within the central DNA-binding domain, we identified a second NLS within the c-Fos N-terminal region. This NLS is non-classic and its activity depends on transportin 1 in vivo. Under conditions of prominent nuclear localization, c-Fos can undergo nucleocytoplasmic shuttling through an active Crm-1 exportin-independent mechanism. Dimerization with the Jun proteins inhibits c-Fos nuclear exit. The strongest effect is observed with c-Jun probably in accordance with the relative stabilities of the different c-Fos:Jun dimers. Retrotransport inhibition is not caused by binding of dimers to DNA and, therefore, is not induced by indirect effects linked to activation of c-Fos target genes. Monomeric, but not dimeric, Jun proteins also shuttle actively. Thus, our work unveils a novel regulation operating on AP-1 by demonstrating that dimerization is crucial, not only for active transcription complex formation, but also for keeping them in the compartment where they exert their transcriptional function.Fil: Malnou, Cécile E.. Centre National de la Recherche Scientifique; FranciaFil: Salem, Tamara Marcela. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Brockly, Frédérique. Centre National de la Recherche Scientifique; FranciaFil: Wodrich, Harald. Centre National de la Recherche Scientifique; FranciaFil: Piechaczyk, Marc. Centre National de la Recherche Scientifique; FranciaFil: Jariel Encontre, Isabelle. Centre National de la Recherche Scientifique; Franci
Harald Sigurdsson and the Russo-Byzantine War of 1043
No full textThe present article analyzes Kekaumenos’ commentary on the service of Harald Sigurdsson in the Byzantine army. Special attention is given to the composition of Consilia et Narrationes and the historiographic perception of this text. It then discusses Kekaumenos’ commentary in light of Harald’s adventures in the Haralds saga Siguðarsonar and the story about the attacks of Rus’ in the Byzantine literature. The author attempts to show that Constantine IX Monomachos tried to leave the large groups of mercenaries in Constantinople. Furthermore, the emperor’s attitude to Harald and his warriors was related to the events of Russo-Byzantine war in 1043. Constantine IX Monomachos dispersed these mercenaries into the themes. John Scylitzes wrote that the emperor put a guard over them to prevent them from inciting a rebellion. These arrests could explain Harald’s mysterious detention in the reign of Constantine IX Monomachos. It is possible to conclude that Harald’s detention was caused by the Russo-Byzantine war in 1043
The fundamental constants: a mystery of physics
No full textThe speed of light, the fine structure constant, and Newton's constant of gravity — these are just three among the many physical constants that define our picture of the world. Where do they come from? Are they constant in time and across space? In this book, physicist and author Harald Fritzsch invites the reader to explore the mystery of the fundamental constants of physics in the company of Isaac Newton, Albert Einstein, and a modern-day physicis
Von der Sorge und Sorglosigkeit : zu Gemeinsamkeiten von Pflege und Tourismus
No full textDieser Beitrag zum Denkanstoß 17 „Zukunft der Pflege“ ergänzt die Beiträge des Denkanstoßes um weitere Aspekte, die nicht in dem Heft berücksichtigt werden konnten. Harald Pechlaner, Giulia Isetti und Michael de Rachewitz erläutern in ihrem Beitrag die Gemeinsamkeiten zwischen den Konzepten von Gastfreundschaft und Pflege (cura)
Menyikapi Keontentikan Hadis Dalam Perspektif Harald Motzki (Studi Isnad Cum Matan Harald Motzki): Id
No full textCurrently, it is still being debated by orientalists about the truth of hadith as a source of Islamic history that is no longer authentically derived from the prophet, as well as the views and thoughts of orientalists in studying hadith such as Ignaz Goldziher and Joseph Schacht which had a great influence on western scientists. The purpose of this study is to repeat the hadith criticism that has been tested by classical hadith scholars that most of the hadiths are not fake as some orientalists understand, the method used is the descriptive analysis of isnad cum matn, in this study the author conducted research by contemporary orientalist Harald Motdzi who broke the previous orientalist hadith critique by proving that from the historical sanad and matn hadith in the book of Musannaf Abd Razaq as-San\u27ani, this study proves that most of the traditions that are sources of law and history are authentic from the Prophet
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